There has recently been a marked increase in abuse and addiction of prescription opioid medications in the U.S., with costly public health consequences. Opioids, such as oxycodone, tend produce feelings of well-being and pleasure (e.g. 'high', elation), and may also reduce negative affect (e.g., relieve emotional distress, relieve anxiety), which may underlie the motives for abuse of opioid prescription drugs. Emerging evidence from affective neuroscience shows that limbic brain regions (e.g., ventral striatum [VS] / nucleus accumbens [NAcc], amygdala) play a pivotal role in the control of emotional experience and motivational behaviors in animals and humans. Interestingly, these regions contain a high density of opioid receptors, and have been posited as critical sites for the reinforcing effects of drugs of abuse. However, the effects of opioid medications on affective experience and emotion-related limbic function in humans are largely unknown. In this study, we propose to evoke positive and negative affect in healthy volunteers using pictures with emotional (and non- emotional/neutral) content. Positive and negative images are associated with increased activity in the VS/NAcc and amygdala, respectively. Our primary aim is to examine if oxycodone changes affective experience and affect-related activation in these limbic brain regions. Subjective affective experience will be measured by self- report ratings of affective valence (ranging from displeasure to pleasure), and limbic brain activity (in the VS / NAcc, amygdala) will be measured by the Blood Oxygenation-Level Dependent (BOLD) signal using functional magnetic resonance imaging (fMRI). These measures will be collected in real-time as subjects are viewing the emotionally-evocative pictures across 3 behavioral-fMRI sessions in a within-subjects, double-blind, randomized, placebo-control, dose-response crossover design following ingestion of placebo (PBO), 10mg, and 20mg of oxycodone. In this project, we bridge the accumulated knowledge and technology from human drug abuse research and brain imaging studies of emotion and affective experience, to test specific hypotheses about the acute effects of an opioid medication with substantial abuse potential on affective experience and associated mesolimbic brain activation. The proposed research directly addresses both the affective/mood-related mechanisms and the neural mechanisms of potential drugs of abuse, to understand why these drugs are misused and abused in nonmedical contexts. Such proof-of-concept findings derived from this study will generate hypotheses for future studies to be conducted in individuals who abuse (or are at risk for abusing) prescription opioid medications. Moreover, the neuroimaging project establishes a network of cross-disciplinary collaboration that will generate findings to support a larger-scale project involving prescription drug abusers or populations at risk for prescription drug abuse. Abuse of prescription pain relievers, such as opioid prescription medications, is a growing public health problem in the U.S. The goal of this project is to examine the effects of oxycodone, one of the more widely abused pain relievers, on mood and on the brain, in order to identify an explanation on why these drugs are being misused, which can help us prevent or treat opioid addiction. [unreadable] [unreadable] [unreadable]